Skin disorders as the term is used herein encompasses numerous skin conditions ranging in severity from severe dermatitis, eczema, psoriasis, etc., which have typically been treated with compositions termed "dermatological" to less severe conditions such as lack of adequate skin firmness, dermal hydration or sebum secretion, etc., which are nonetheless unsightly and may cause physical discomfort. The latter type of skin disorders typically have been treated with compositions termed "cosmetic" which are used with the aim of preserving, conditioning or protecting the skin. Dermatological and cosmetic preparations have long been sought which are effective in the topical treatment of such skin disorders and which do not produce untoward side effects, including both systemic effects and such local effects as decreased skin elasticity.
Hitherto the treatment of skin disorders has been largely based on non-specific drugs, and only limited success has been achieved. Dermatitis, for example, which may be accompanied by severe scaling, fissures, edema, oozing, erosion, itching and thickening of the skin has been commonly treated with corticosteriods. Such compounds provide symptomatic relief for some patients. Steroids, however, are known to produce many local and systemic side effects, and their long term use may not be desirable.
Similarly, Vitamin D is therapeutically effective in treating certain skin disorders, but only as dosages which are associated with undesirable side effects. Vitamin D at the dose ranges used in currently marketed topical preparations is not therapeutically effective against contact dermatitis.
Prior to this invention, no compositions were known for the topical treatment of the above-mentioned skin disorders which contain materials having both calciferol-related structure and high activity in the induction of calcium binding protein. While there has been extensive use of fish liver oil, which is rich in cholecalciferol, and of various other preparations containing ergocalciferol or cholecalciferol, such preparations are known to have only limited activity.
Ergocalciferol and cholecalciferol have also been used topically as general healing and soothing preparations, usually in concentrations no greater than five (5) micrograms/g because of concern for side effects. Such preparations, however, have achieved clinical results of only low efficacy. One possible reason for the limited efficacy of these preparations, although the inventors do not wish to be bound by this theory, is that ergocalciferol and cholecalciferol have a low potency for inducing calcium binding protein. It is known that an increase in the calcium binding protein level increases the concentration of intracellular calcium in skin cells, which in turn increases the cyclic-AMP content of the cells, see Corradino, Endocrinol., 94: 1607 (1974).
Low cyclic-AMP concentrations in skin cells are known to be associated with certain skin disorders such as psoriasis, dermatitis and alopecia. The inventors have found that low cyclic-AMP levels are also encountered in various other skin disorders such as undue skin softness and slackening of the skin. Attempts to increase the cyclic-AMP content of the skin have been described in the literature.
In pursuing this approach to the study of skin disorders, the inventors have unexpectedly discovered that particular cholecalciferol derivatives are highly effective in the treatment of certain skin disorders.